Over the past 16 years, we have established a unique, population-based study of non-melanoma skin cancer in New Hampshire that has made important scientific and public health contributions and informed policy decisions. Basal cell carcinoma (BCC) and squamous cell skin carcinoma (SCC), collectively termed non- melanoma skin cancer (NMSC), comprise the mostly frequently diagnosed cancers in the US. Consequently, these malignancies account for substantial morbidity, disfigurement and health care costs. However, few population-based epidemiologic studies exist in the US or globally. In the past three decades, both major types of NMSC - BCC and SCC - have increased dramatically. Of particular concern is accumulating evidence of a substantial rise in the occurrence of BCC at younger ages, for reasons not yet identified. It is imperative to measure and establish the risk factors that underlie this trend as these individuals not only have an increased likelihood of developing additional NMSCs, but invasive cutaneous melanomas and other malignancies as well. Building on our established population-based study of NMSCs, we will determine whether incidence rates of early-onset BCC have continued to increase. Further, we will investigate whether developing a BCC at an early age is due to emerging factors e.g., use of newer generation tanning devices, photosensitizing drugs, immunosuppressive agents and other nascent exposures. We will determine whether melanoma-related traits influence risk of early-onset BCCs including number of nevi and family history of melanoma. To investigate these new hypotheses, we will conduct targeted enrollment of new cases and controls (an additional 550 cases and 600 controls). This will entail continuing our collaborative, state-wide case ascertainment network of dermatologists, dermatopathologists and pathologists, which simultaneously allows us to measure incidence rates. Residents of New Hampshire newly diagnosed with BCC before age 50 years will be prospectively identified through this surveillance system. Age and sex frequency matched controls will be selected from New Hampshire driver's license records. We will conduct a standardized personal interview encompassing exposures of interest along with a complete assessment of sun exposure history, sun sensitivity and pigmentary traits, and will archive a blood (or buccal) sample. Pooling data from the previous grant period will permit us to test hypotheses with statistical power not otherwise possible, providing a cumulative total of approximately 1,200 early-onset BCC cases and 1,200 controls. Using our comprehensive approach, we can address an emerging public health concern, determine avoidable risk factors for the most common cancer in the US, and aid the discovery of new risk factors for other malignancies. PUBLIC HEALTH RELEVANCE: Recent evidence suggests that basal cell carcinomas, the most common cancer in humans, are becoming more widespread among younger adults and women, for reasons as yet unknown; however, because this type of cancer is not routinely monitored in the US, we have limited information about their occurrence and risk factors. Our goal is to fill this important gap by leveraging our long-standing study of skin cancer in a US population. We propose to estimate the current rates and trends in these tumors and to help identify the underlying causes of their occurrence.